Tissue biopsy and treatment apparatus and method

ABSTRACT

A method of treating a tumor includes providing a tissue biopsy and treatment apparatus that includes an elongated delivery device that has a lumen and is maneuverable in tissue. A sensor array having a plurality of resilient members is deployable from the elongated delivery device. At least one of the plurality of resilient members is positionable in the elongated delivery device in a compacted state and deployable with curvature into tissue from the elongated delivery device in a deployed state. At least one of the plurality of resilient members includes at least one of a sensor, a tissue piercing distal end or a lumen. The sensor array has a geometric configuration adapted to volumetrically sample tissue at a tissue site to differentiate or identify tissue at the tissue site. At least one energy delivery device is coupled to one of the sensor array, at least one of the plurality of resilient members or the elongated delivery device. The apparatus is then introduced into a target tissue site. The sensor array is then utilized to distinguish a tissue type. The tissue type information derived from the sensor array is utilized to position the energy delivery device to ablate a tumor volume. Energy is then delivered from the energy delivery device to ablate or necrose at least a portion of the tumor volume. The sensor array is then utilized to determine an amount of tumor volume ablation.

CROSS-RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S.Provisional Application Ser. No. 60/193,544 filed Mar. 31, 2000,entitled “Tissue Biopsy, Monitoring and Treatment Apparatus and Method”,which is fully incorporated by reference herein. This application isalso related to a co-pending application attorney docket number13724-844.

FIELD OF THE INVENTION

[0002] This invention relates generally to a method for performing an invivo tissue biopsy sample using minimally invasive methods. Moreparticularly, the invention to relates to method and apparatus forperforming in vivo tissue biopsy using optical methods. Still moreparticularly, the invention relates to a method and apparatus forperforming an in vivo tissue biopsy to discriminate between diseased andhealthy tissue and facilitate tissue treatment.

BACKGROUND OF THE INVENTION

[0003] Various ablative procedures can be used to treat diseased and/orabnormal tissue. These methods cause physiological and structuralchanges intended to cause necrosis of the selected target tissue. Duringablative procedures of diseased and other abnormal tissue, cliniciansencounter numerous difficulties and challenges, these include (i)locating the target tissue, (ii) the need to perform a biopsy anddiagnose diseased tissue versus healthy tissue, (iii) correct deviceplacement, (iv) monitoring ablation progress, (v) assuring a (healthytissue) margin, and (vi) assessing the completed ablation. Currentablative technologies have failed to recognize and therefore, properlyaddress these requirements.

SUMMARY OF THE INVENTION

[0004] An embodiment of the invention provides a method of treating atumor that includes providing a tissue biopsy and treatment apparatusthat includes an elongated delivery device that has a lumen and ismaneuverable in tissue. A sensor array having a plurality of resilientmembers is deployable from the elongated delivery device. At least oneof the plurality of resilient members is positionable in the elongateddelivery device in a compacted state and deployable with curvature intotissue from the elongated delivery device in a deployed state. At leastone of the plurality of resilient members includes at least one of asensor, a tissue piercing distal end or a lumen. The sensor array has ageometric configuration adapted to volumetrically sample tissue at atissue site to differentiate or identify tissue at the tissue site. Atleast one energy delivery device is coupled to one of the sensor array,at least one of the plurality of resilient members or the elongateddelivery device. The apparatus is then introduced into a target tissuesite. The sensor array is then utilized to distinguish a tissue type.The tissue type information derived from the sensor array is utilized toposition the energy delivery device to ablate a tumor volume. Energy isthen delivered from the energy delivery device to ablate or necrose atleast a portion of the tumor volume. The sensor array is then utilizedto determine an amount of tumor volume ablation.

[0005] An embodiment of the invention provides a tissue biopsy andtreatment apparatus that comprises an elongated delivery device that ispositionable in tissue and includes a lumen. A sensor array having aplurality of resilient members is deployable from the elongated deliverydevice. At least one of the plurality of resilient members ispositionable in the elongated delivery device in a compacted state anddeployable with curvature into tissue from the elongated delivery devicein a deployed state. At least one of the plurality of resilient membersincludes at least one of a sensor, a tissue piercing distal end or alumen, The sensor array has a geometric configuration adapted tovolumetrically sample tissue at a tissue site to differentiate oridentify tissue at the target tissue site. At least one energy deliverydevice is coupled to one of the sensor array, at least one of theplurality of resilient members or the elongated delivery device.

[0006] Yet another embodiment of the invention provides a method fortumor detection, wherein a primary optically labeled marker or antibodyis infused into a patient or injected into a target tissue or organ sitecontaining a tumor and specifically binds to a marker produced by orassociated with a tumor. The target tissue or organ site is scanned witha biopsy ablation apparatus including a sensor array and the bindingsites of the labeled marker antibody are located by detecting elevatedlevels of optical label signal intensity at such sites with the sensorarray. This information can be digitally stored and displayed on amonitor device to accurately position the biopsy ablation apparatuswithin the tumor s to deliver energy to necrose or ablate the tumorresulting in an ablation volume. A second marker which binds or reactswith necrosed tumor tissue can infused or injected into the tumor sitebefore, during or after the delivery of ablating energy. The sensorarray is utilized to detect the signal from the second marker ablationvolume and this signal digitally stored and superimposedly display overtumor volume image so as to determine the size of the ablation volumerelative to the tumor volume. This embodiment provides two key benefitto the physician: (i) visual confirmation that the tumor has beencompletely ablated/necrosed, (ii) selective over control the amount ofhealthy tissue margin that is ablated beyond the tumor volume to improveclinical outcomes of the procedure.

BRIEF DESCRIPTION OF THE FIGURES

[0007]FIG. 1 is a lateral view illustrating the placement of anembodiment of a tissue biopsy and treatment apparatus at a tissue site.

[0008]FIG. 2 is a lateral view illustrating the components of anembodiment of a biopsy and treatment apparatus including the elongatedmember, sensor array, resilient members and energy delivery device andadvancement member.

[0009]FIGS. 3a and 3 b are cross sectional and perspective viewsillustrating embodiments of the resilient member having a slot.

[0010]FIG. 3c is a perspective view illustrating an embodiment of thesensing member fixedly positioned to the resilient member.

[0011]FIG. 4 is a perspective view illustrating an embodiment of abiopsy and treatment apparatus having an emitting member and detectingmember positionable positionable in the resilient member.

[0012]FIG. 5 is a schematic view illustrating various optical tissueinteractions and properties.

[0013]FIG. 6 is a perspective view illustrating an embodiment thesensing members fixedly positioned within the resilient member.

[0014]FIG. 7 is a perspective view illustrating the use of differentwavelengths to sample multiple tissue volumes in an embodiment of theinvention.

[0015]FIGS. 8a-8 d are perspective views illustrating variousarrangements of the emitting and detecting members;

[0016]FIG. 8a illustrates an embodiment having a centrally positionedemitter member surrounded by detector members;

[0017]FIG. 8b illustrates an embodiment having centrally a positioneddetector member surrounded by emitter members;

[0018]FIG. 8c illustrates an embodiment having emitters 22 me anddetectors 22 md located in linear arrangements that are substantiallyperpendicular or have a selectable angle;

[0019]FIG. 8d illustrates an embodiment having multiple andindependently positionable and rotatable sensor arrays.

[0020]FIG. 9 is a perspective view illustrating an embodiment of abiopsy and treatment apparatus having sensors members positionabledistally to the energy delivery member.

[0021]FIG. 10 is a perspective view illustrating an embodiment of theinvention having a multiple wavelength laser light source.

[0022]FIG. 11 is a perspective view illustrating use of an opticalmarker compound and binding agent in an embodiment of the invention.

[0023]FIG. 12 is a perspective view illustrating an embodiment of abiopsy and treatment apparatus configured to detect metabolicchromophores.

[0024]FIG. 13 is a perspective view illustrating an embodiment of abiopsy and treatment apparatus configured to generate a 3D map of thetumor.

[0025]FIG. 14a is a perspective view illustrating use of sensor array tomonitor a developing ablation volume.

[0026]FIG. 14b is a plot of spectral signal intensity verses time for asample volume of ablating tissue illustrating quantitative determinantsof an ablation endpoint.

[0027]FIG. 15 is a lateral view illustrating a control and display unitused in various embodiments of the invention.

[0028]FIGS. 16a-16 c are perspective views illustrating use of thesensor array to assure proper placement of the energy delivery membersin the tumor mass in an embodiment of a method of the invention.

[0029]FIGS. 17a and 17 b are perspective views illustrating use of thesensor array to detect an incomplete ablation in embodiments of a methodof the invention.

[0030]FIG. 18a is a lateral view illustrating the configuration of theintroducer.

[0031]FIGS. 18b and 18 c are cross sectional views illustratingcross-sectional profiles of the introducer.

[0032]FIG. 19 is a lateral view illustrating an embodiment of adeflectable introducer along with the components of the introducer.

[0033]FIG. 20 is a lateral view illustrating an embodiment of a tissuebiopsy and treatment apparatus with a handpiece and coupled aspirationdevice, fluid delivery device and fluid reservoir

[0034]FIGS. 21a-21 f are lateral views illustrating variousconfigurations of the electrode including ring-like, ball,hemispherical, cylindrical, conical and needle-like.

[0035]FIG. 22 is lateral view illustrating an embodiment of a needleelectrode configured to penetrate tissue.

[0036]FIG. 23 is lateral view illustrating an embodiment of an electrodehaving at least one radii of curvature.

[0037]FIG. 24 is lateral view illustrating an embodiment of theelectrode having a radii of curvature, sensors and a coupled advancementdevice.

[0038]FIG. 25 is a perspective view illustrating an embodiment of theelectrode that includes insulation sleeves positioned at exteriorsurfaces of the electrode(s) so as to define an energy delivery surface.

[0039]FIG. 26 is a perspective view illustrating an embodiment of theelectrode that includes multiple insulation sleeves thatcircumferentially insulate selected sections of the electrode(s).

[0040]FIG. 27 is a perspective view illustrating an embodiment of theelectrode with insulation that extends along longitudinal sections ofthe electrodes to define adjacent longitudinal energy delivery surfaces.

[0041]FIG. 28 is a cross-sectional view of the embodiment of FIG. 27.

[0042]FIG. 29 is a lateral view illustrating an embodiment of theapparatus with an electrode having a lumen and apertures configured forthe delivery of fluid and the use of infused fluid to create an enhancedelectrode.

[0043]FIG. 30 is a block diagram illustrating a controller, powersource, power circuits and other electronic components used with anembodiment of a control system other embodiments of the invention.

[0044]FIG. 31 is a block diagram illustrating an analog amplifier,multiplexer and microprocessor used with an embodiment of a controlsystem or other embodiments of the invention.

DETAILED DESCRIPTION

[0045] Embodiments of the present invention provide a method andapparatus to optically biopsy a tissue and use the information todiagnose a tumor, accurately position an energy delivery device,visually monitor and confirm complete ablation of the tumor. Furtherembodiments of the invention include one or more sensing members orsensing arrays that can be deployed independently or simultaneously toenable probing of target tissue by optical or other means. Deployment ofeach array is controlled such that telemetry can be used with optical,temperature and impedance feedback to both identify tissue and map thetopography of tissue types and structures to facilitate proper placementof an energy delivery device to ablate the tumor. These and otherembodiments of the invention allow for the control and determination ofa clinical endpoint while significantly reducing the risk of incompleteablation or unwanted damage to critical anatomical structures due toimproper device placement.

[0046] Specific embodiments are configured to utilize inputs from thesensor to distinguish and identify the distinct spectral profiles thatare generated by different tissues. The apparatus is further configuredto employ analytical methods to compare these profiles and utilize themto accurately identify and distinguish between tissue types. Such tissuecomparison and identification is particularly applicable to thedetection of metastases and other types of tumors. This is due to thefact that metastases are growths of tissue from cells originating in adifferent part of the body from the subsequent tumor site that theycause. As such these different body tissues have different pathologicalfeatures, the spectral profile comparison can be used to discern ametastatic or other non-native tumor within the target tissue sample.

[0047]FIG. 1 shows an embodiment of a tissue biopsy and treatmentapparatus 10 configured to optically biopsy and treat a tumor mass 5″ ina target tissue site 5′ by volumetrically sampling the tissue mass anddelivering energy or other treatment to produce an ablation volume 5 av.Referring now to FIGS. 1 and 2, an embodiment of biopsy treatmentapparatus 10 comprises an elongated member or introducer 12 having alumen 13, a proximal portion 14, a distal end 16, one or more resilientmembers 18 positionable in lumens 13 and one or more sensing members 22m positionabe in lumens 72 disposed within members 18. Distal end 16 maybe sufficiently sharp to penetrate tissue including fibrous and/orencapsulated tumor masses, bone, cartilage and muscle. Lumens 13 mayextend over all or a portion of the length of introducer 12. Members 18can comprise a plurality 18 pl of resilient members 18 configured to bepositionable in lumen 13 and advanceable in and out of distal end 16 byan advancement device 15 or advancement member 34 or other meansdescribed herein. Resilient members 18 can be deployed with curvaturefrom introducer 12 to collectively define a volume 5 av in target tissuesite 5′. In an embodiment all, or a portion, of one or more members 18can be an energy delivery device or energy delivery member 18 edescribed herein. Energy delivery device 18 e can be coupled to anenergy source or power supply 20 and can also include one or more lumens72.

[0048] In various embodiments, introducer 12 can be flexible,articulated and steerable and can contain fiber optics (bothillumination and imaging fibers), fluid and gas paths, and sensor andelectronic cabling. In an embodiment introducer 12 can be configured toboth pierce tissue and also be maneuverable within tissue. This can beachieved through the use of flexible portions coupled to a tissuepiercing distal end 16 that can be a needle or trocar tip integral orjoined to introducer 12. Introducer 12 can be sufficiently flexible tomove in any desired direction through tissue to a desired tissue site5′. In related embodiments, introducer 12 is sufficiently flexible toreverse its direction of travel and move in direction back upon itself.This can be achieved through the use of flexible materials and/ordeflecting mechanisms described herein. Also, introducer 12 can becoupled at its proximal end 14 to a handle 24 or handpiece 24. Handpiece24 can be detachable and can include ports 24′ and actuators 24″.

[0049] One or more sensors 22 can be coupled to introducer 12, resilientmembers 18 or energy delivery device 18 e. In an embodiment, sensors 22can comprise one or more sensing members 22 m that can be positionablewithin lumens 72 of members 18 and configured to be advanceable in andout of individual members 18 or can be coupled to an exterior ofresilient member 18. Sensing members 22 m can comprise a plurality ofmembers 22 mpl positioned in multiple resilient members 18 Sensingmembers 22 m, or sensors 22 coupled to resilient members 18 can bedeployed independently or simultaneously to enable probing of targettissue 5′ in multiple locations. Deployment of sensing member 22 m orsensors 22 can be controlled such that telemetry can be used withoptical temperature and impedance feedback to identify tissue types andmap the topography of tissue masses, tumors or tissue structures.

[0050] 33. Sensing members 22 m can also be deployed with curvature frommembers 18 to collectively define a volume 5 sv (also called samplevolume 5 sv) that is volumetrically sampled by sensing member plurality22 mpl. Collectively, the plurality 22 mp of deployed sensor members 22m or plurality 18 pl of deployed resilient members 18 with coupledsensors 22 can comprise a 3 dimensional or volumetric sensor array 22 a.By having sensors 22 in multiple locations and planes sensor array 22 ais configured to volumetrically sample (e.g. sample in multiplelocations) tissue within target tissue site 5′ including tumor mass 5″.Sensor array 22 a is further configured to be able to simultaneouslysample tissue at multiple locations within volume 5 sv or tissue site 5′to perform one or more of the following: (i) locate the position of thetumor mass 5″, (ii) discern the position or deployment distance of theenergy delivery devices 18, (iii) monitor the developing ablationvolume, (iv) perform tissue sensing biopsy and identification bycomparing signals between two or more site (e.g. known healthy tissueand suspected diseased tissue). In various embodiments sensor array 22 aand/or member plurality 18 pl can be configured to define a variety ofshapes for sample volumes 5 sv including, but not limited to, ahemisphere, a sphere, an oval, a cone, pyramidal, a polyhedron or atetrahedron.

[0051] Referring now to FIGS. 3a and 3 b, in an alternative embodimentsensor member 22 m can be advanced through a slot 72 s in or on thesurface of resilient member 18. Slot 72 s serves as track to guide andadvance sensor member 22 m. Slot 72 also serves to increase thetorsional flexibility of member 18 and to lesser extent lateralflexibility (the reciprocal of stiffness). The size and shape of slot 72s can also configured to increase the lateral flexibility of member 18with a minimal affect on lateral flexibility (e.g. less than 10%).Shapes for slot 72 s can include but are not limited to substantiallysemi-ovoid or semi-circular. In various embodiments the torsionalflexibility of member 18 can be increased in the range of 10 to 200%with specific embodiments of 25, 50 and 100% with increases in lateralflexibility being lower in each case. Also in various embodiments, thetorsional flexibility of member 18 can be controllably adjusted via thelength of sensor member 22 m positioned within slot 72 s. In oneembodiment member 18 with a slot 72 has a maximum flexibility when slot72 is empty, as increasing lengths of sensor member 22 m are advancedwithin slot 72 member 18 flexibility is decreased until sensor member 22m completely fills slot 72 s. In a related embodiment shown in FIG. 3c,sensing members 22 m can be fixedly attached to the exterior ofresilient member 22 either in slot 72 s or adhered to the surface ofmember 18 using an adhesive known in the art.

[0052] In various embodiments, multiple sensing members 22 m can bepositioned and deployed from a single lumen 72 of resilient member 18and/or from lumen 13 of introducer 12. Referring now to FIGS. 4 and 5,in an embodiment, two sensing members 22 m can be positioned in a lumen72 of one or more resilient members 18: a light emitting member 22 me,configured to emit an incident or probe beam 22 ib; and a lightdetecting member 22 md, configured to detect returning light 22 rbresulting from various optical tissue interactions (including scatter,reflectance or absorbance) of incident beam 22 ib by tissue 5 as isshown in FIG. 5.

[0053] In these and other embodiments members 22 m, 22 me and 22 md canbe optical fibers including glass fiber known in the art such as thosemanufactured by the Dow Corning Corporation (Midland, Michigan) orPolymicro Technologies (Phoenix, Ariz.). The diameter 22 d of fiber 22 mcan be in the range of 0.001 to 0.010″ with a preferred embodiment ofabout 0.004″ (without cladding). When light emitting member 22 me is afiber optic, one or more members 22 me can include or be coupled(preferably at its distal end 22 med) to a collimating or focusing lens221 to collimate, and/or increase or decrease the size of incident beam22 ib. Similarly light detecting fiber 22 md can include or be coupledto a collimating lens 22 l preferably at the proximal end 22 mdp ofmember 22 to collimate returning light prior 22 rb prior to its entryinto a optical measurement device described herein.

[0054] In an alternative embodiment shown in FIG. 6, sensing members 22including emitting member 22 me and detecting member 22 md 22 me can befixedly positioned within resilient member 18 such that their distalends are substantially flush with the distal end 18 de of resilientmember 18 or can fixed in other arrangements such as protruding slightlyout of distal end 18 de by several thousandths of inch or more or beingrecessed by a similar amount within distal end 18 de. These embodimentsprovide the benefit of maintaining the optical relationship between theemitting and detecting members 22 me and 22 md constant, reducing signalvariations due to movement of either member. In a related embodiment,sensing members 22 me and 22 me can also be fixedly positioned at ornear the distal end 16 of introducer 12.

[0055] Sensing members 22 can be arranged in variety of configurationsto perform one or more desired functions (e.g. tissue identification).Each resilient member 18 can have one or more sensing members 22. Somemembers 18 may have emitters 22 me and some detectors 22 md, so thatselectable portions of tissue between members 18 can be interrogated viadifferent optical paths. Emitters 22 me and detectors 22 md can bepositioned anywhere within or outside of members 18 including at thetips 18 de of members 18 where they can be fixedly positioned.Alternative embodiments may comprise emitters 22 me and detectors 22 mdpositioned on passive or otherwise non-energy delivery resilient members18 so as to position at least some of the emitter and detectors beyondthe developing or complete ablation volume 5 sv. Such configurationsallow for monitoring outside of tissue outside of the developingablation volume to simultaneously compare un-ablated tissue 5 andablated tissue 5 av as well as reduce signal noise and artifacts fromenergy delivery within the ablation volume.

[0056] Referring back to FIGS. 2 and 4, in various embodiments one ormore sensing member 22 m can coupled to an optical switching device 29or otherwise configured such that their function can be dynamicallyswitched from an emitter to a detector mode and vice versa. By changingthe optical function of sensing member 22 m (e.g. from receiving toemitting) during the process of scanning or interrogating a desiredtissue sample volume 5 sv, directional biases, signal artifacts anddetection errors can be reduced improving detection sensitivity.Further, different emitter detector combinations can be employed toobtain more accurate higher resolution signals and hence more detailedinformation about the target tissue. When both emitter member 22 me anddetecting member 22 md are located in the same member 18, they can beoperated simultaneously for localized tissue sampling and interrogation.Such configurations allow for the comparison of tissue adjacent oneresilient member 18′ to that of another resilient member 18″. In arelated embodiment, emitting or detecting sensing members 22 on multipleand/or distant resilient members 18 can be operated collectively toobtain a more global interrogation of a desired sample volume 5 sv usingone or more wavelengths.

[0057] In various embodiments separate wavelengths can be used tosimultaneously sample different locations within target tissue site 5′.In an embodiment shown in FIG. 7 a first interrogation wavelength orgroup of wavelengths 7′ can be used to sample a local first volume 5 sv1 and a second wavelength or group wavelengths 7″ for a second volume 5sv 2 and a third wavelength for larger or global sample volume 5 sv 3defined or circumscribed by multiple sensor tipped members 18 or sensingmembers 22. Each sample volume 5 sv probed with a given wavelength 7results in a separate spectral profile 19 s. Thus sample volumes 5 sv 1,5 sv 2 and 5 sv 3 produce spectral profiles 19 s 1, 19 s 2 and 19 s 3respectively.

[0058] Referring now to FIGS. 8a-8 d, in various embodiments lightemitting members 22 me and light detecting members 22 md can be arrangedin arrays 22 a having a variety of geometric arrangements andrelationships so as to optically sample different volumes of tissue 5 svusing different optical paths and/or optical tissue interactions. Suchembodiments provide the benefit of improved acquisition, accuracy andanalysis of the spectral signal 19 s from a given sample volume 5 sv tocompensate for signal hysteresis, noise (due to energy delivery etc)directional bias or other error They also provide the benefit ofsimultaneous sampling and comparison of two or more tissue volumes toperform tissue identifications. In an embodiment shown in FIG. 8a anemitting member 22 me is positioned at the center of tissue volume 5 svwith detecting members or sensor 22 md positioned in a surroundingrelationship so light passes from the center of the sample volume to theoutlying sensors. In another embodiment shown in FIG. 8b, a detectingmember 22 md is positioned at the center of tissue volume 5 sv withemitting members 22 me or sensors 22 positioned in a surroundingrelationship so as to transmit light inward. In yet another relatedembodiment shown in FIG. 8c, emitters 22 me and detectors 22 md can belocated in a linear arrangements 22′ that are substantiallyperpendicular or have another selectable angle 22″. Alternatively asshown FIG. 8d, emitters 22 me can comprise a first array 22 a 1 (such asperpendicular array) and the detector 22 md located on a separate array22 a 2. First array 22 a 1 can be rotated to obtain different opticalpaths to detector array 22 a 2 so as to sample different tissue volumesand/or provide multiple samplings of the same volume (via differentoptical paths) to improve accuracy and signal to noise ratios.

[0059] In another embodiment shown in FIG. 9, one or more sensor members22 m can be advanced from energy delivery member 18 e so as to bepositioned a selectable distance 45 distal to the distal end 18 de ofenergy delivery member 18 e (which corresponds to the deploymentdistance 43 of energy delivery member 18.). Distance 45 onto or evenbeyond the point that member 22 m is positioned outside of the ablationvolume 5 sv. Distance 45 can be a greater longitudinal distance 45′ or alateral distance 45″ with respect to a longitudinal axis 12 a 1 ofintroducer 12. This can also be achieved by the embodiment shown in FIG.8d utilizing two or more arrays 22 a, with at least one array positionedoutside of the ablation volume.

[0060] Referring back to FIG. 4, emitting member 22 me can include anintegral light source 17 such as an LED or a diode laser oralternatively can be optically coupled to an external light source 17which in various embodiments, can be configured to emit light atmultiple wavelengths and over a range of wavelengths including, butlimited to the range of 300 to 850 nm, a more preferred range of 450 to850 nm with specific embodiments in the UV and infrared ranges. In anembodiment light source 17 can be a monochrometer known in the art.Examples of monchrometers include single crystal, double crystal andsurface normal reflection monchrometers as well as models manufacturedby Macken Instruments Inc. (Santa Rosa, Calif.). In other embodiments,light source 17 can be a white light source, a xenon bulb, an LED or acoherent light source such as a laser configured to emit probe beam 22ib. Examples of lasers include, but are not limited to, YAG lasers,Nd:YAG lasers, CO₂ lasers, infrared lasers, argon lasers, tunable dyelasers and copper vapor lasers. Referring now to FIG. 10, laser device17 can include multiple beams at different wavelengths including a first22 ib′ and a second beam 22 ib″ having a first and second wavelength 7′and 7″ wavelength. Examples of multiple wavelength emitting lasersinclude CO₂ lasers and argon-pumped tunable dye lasers. The use ofmultiple and/or a broad spectrum of wavelengths 7 provides the benefitof increased tissue or tissue chromophore specificity and henceincreased predictive power (e.g. statistical confidence) of associatedtissue identification algorithms described herein. The use of laserlight source 17 with multiple beams and wavelengths can also beconfigured to determine the deployment distance of one or more members18, 18 e using laser range finding methods known in the art.

[0061] Referring back to FIG. 4, in an embodiment detecting member 22 mdcan be coupled to an optical measurement device 19 such as aspectrophotometer, reflectometry device or CDC device. For ease ofdiscussion, optical measurement device will now be referred to as aspectrophotometer, but all other embodiments are equally applicable.Spectrophotometer device 19 is configured to detect and record spectralinformation including a tissue spectra or spectral profile 19 sresulting from optically induced tissue interactions such asreflectance, transmittance and scatter resulting from the incident light22 i from emitter 22 me on tissue within sample volume 5 sv.

[0062] In an embodiment, spectrophotometer device 19 can include logicresources 19 lr such as a microprocessor and memory resources 19 lr suchas RAM or DRAM chip configured to analyze, store and display tissuespectral profile 19 s and/or other optical information derived fromsensing member 22 m and/or sensing array 22 a. Spectrophotometer device19 can also be coupled to a display device 21 so as to display real timeor stored spectra, images and other data generated by spectrophotometerdevice 19. Examples of display devices 22 include cathode ray tubes(CRTs), liquid crystal displays, plasma displays, flat panel displaysand the like. Display device 22 can also be incorporated in an externalcomputer 24 coupled to spectrophotometer device 19.

[0063] Referring now to FIG. 11, in various embodiments light source 17can also include a wavelength 7 f configured to cause fluorescence of anoptical marker compound or molecule 9 either naturally occurring orcoupled to a tumor specific binding agent 9 ba such as an antibody,protein or liposome known in the art. Antibody 9 ba is configured toattach to a tumor specific antigen 9 a. Binding agent 9 ba can also beconfigure to be controllably release marker 9 when a specific tissuecondition is met such as temperature, release of intracellularfluids/contents or other indications of cell lysis from ablativetreatment. Binding agent 9 ba can include a plurality of binding agents9 ba including a first and a second binding agents 9 ba 1, 9 ba 2configured to be released a first and a second marker 9′ and 9″ upon afirst tissue condition and a second tissue condition. An example ofbinding agent that is configured to controllably release a markerincludes a liposome. Suitable liposomes include those manufactured byLiposome Technology Inc. (Menlo Park, Calif.). In various embodimentsbinding agents 9 ba, 9 ba 1 or 9 ba 2 can be configured to releasemarker 9 in a temperature range from about 40° C. to about 60° C.; andmore preferably in the range from about 45° C. to about 55° C. Marker 9can also be configured to enhance the delivery of energy to tumor 5″ andor increase the necrotic effect of energy on the tumor mass. An exampleof an energy delivery enhancing marker is an ferro-colloid compound.

[0064] In an embodiment, marker 9 and binding agent 9 ba can be mixed ina solution 27 that is fluidically coupled to introducer 12 (via areservoir or fluid delivery device described herein) and delivered totissue site 5′ through lumen 13 of introducer 12 or through lumen 72 ofmember 18.

[0065] In related embodiments, markers 9 can be configured to degradeupon a given tissue condition such that a decrease in the concentrationof marker 9 serves as an indicator of that tissue condition, temperaturebeing one example. In various embodiments, marker 9 can be configured todegrade or under a change in state or phase (e.g. solidify liquefy orvaporize) upon a number of conditions or tissue treatments including:temperature or thermal irradiation, electrical current such as an RFcurrent, ultrasound irradiation, UV radiation, ionizing irradiation andthe like. These and related embodiments can be configured to be used inconjunction with an analytical method known in the art such asfluorescence spectroscopy described herein.

[0066] In various embodiments apparatus 10 and array 22 a includingmembers 22 m can be configured to perform tissue identification,differentiation, ablation monitoring and mapping of tissue masses andstructures. In specific embodiments, apparatus 10 is configured toperform a tissue biopsy function using optical or other informationderived from array 22 a. Such information is obtained by probing thetarget tissue volume 5 sv with an incident beam 22 ib having one or morewavelengths 7. As described herein, the optical tissue interactions ofincident beam 22 ib on target tissue site 5′ result in a distinctspectral profile 19 s that serves as a fingerprint of the tissue type.As shown in FIG. 5 the main optical tissue interactions include scatter,reflection and absorption and to a lesser extent fluorescence. Referringback to FIG. 4, these optical tissue interactions are controlled to alarge extent by chromophores 33 that result in one or more peaks 33 pwithin profile 19 s. Chromophores 33 can include metabolic chromophores33 that are individually or collectively predictive of a particulartissue type including cancerous tissue. By analyzing and matching peaks33 p corresponding to one or more of these chromophores 33, spectralprofile 19 s has predictive value for tissue type and/or a tissuecondition such as necrosis or thermal injury. Further, many tissue typeswill have a signature profile 19 s that can be readily identified andmatched to a database of profiles using pattern recognition techniquesor algorithms known in the art including fuzzy logic methods.Accordingly, apparatus 10 including sensor array 22 a can be configuredto generate and analyze a composite spectral profile 19 s includingreflectance, absorption and fluorescence components depending on thetissue type and associated chromophores of interest. Alternatively,apparatus 10 can sensor array 22 a can be configured to generate andanalyze individual spectral profiles 19 s for a particular opticalproperty, again depending on the chromophores of interest.

[0067] Referring still to FIG. 4, in various embodiments, apparatus 10can include electronic algorithms or software modules 19 m resident inlogic resources 19 lr of device 19 or microprocessor 339 that areconfigured to analyze profile 19 s and perform tissue identificationand/or tissue differentiation between one or more sampled volumes 5 sv.Modules 19 m can include pattern recognition algorithms or fuzzy logic.Also in an embodiment, modules 19 m can be configured to compare profile19 s to a database of profiles 19 db stored in memory resources 19 mruse curve fitting or other numerical methods known in the art to provideand display a correlation coefficient or statistic indicative of theprobability of a match to a particular tissue type.

[0068] Referring now to FIG. 12, in various embodiments apparatus 10 canalso be configured to differentiate cancerous or other abnormal tissuevs. healthy tissue based on metabolic abnormalities of cancerous tissue.Accordingly in various embodiment, apparatus 10 and arrays 22 a can alsobe configured to detect and/or quantify specific chromophores 33including metabolic chromophores 33, also called metabolites 33 that arepredictive or otherwise indicative of cancerous tissue, precanceroustissue, abnormal tissue, necrosed tissue or injured tissue. In anembodiment, apparatus 10 can be configured to detect and/or quantify aplurality of metabolites 33 p that can include a first, second, thirdand fourth metabolite, 33 a, 33 b, 33 c, and 33 d. Software module 19 acan compare detected metabolite concentrations for one or mores of thesemetabolites to a database of 19 dp of metabolite concentrations forknown cancer types and use curve fitting, fuzzy logic or other numericalmethods to establish a match along with an associated confidence metricsuch as a p-value. In an alternative embodiment, apparatus 10 includingmodule 19 a can be configured to utilize relative differences inconcentrations of metabolites 33 by detecting and measuringconcentrations of metabolites in a first sample volume 5 sv 1 containinghealthy tissue can compare those to measurements for cancer metabolites33′ of a second sample volume 5 sv 2 believed to be a tumor or canceroustissue volume 5″. Module 19 m can calculate the differences and compareone or more of them to a database 19 db of differences for known cancertypes and use curve fitting, fuzzy logic other numerical methods toestablish a match along with an associated confidence metric.

[0069] In a related embodiment, emitter 22 me can also be configured toemit a reference beam 22 ref at a reference wavelength 7 r that does notappreciably interact with the target chromophore 33 so as to compensatefor tissue hysteresis. In another related embodiment spectrophotometrydevice 19 can be a dual beam spectrophotometer in which a reference beam22 ref is also used to compensate for any hysteresis in the light source17.

[0070] In various embodiments, predictive metabolites 33 include, butare not limited to, oxyhemoglobin, deoxyhemoglobin DNA and DNAfragments, tissue oxygen or PO₂, lipids, glucose, acids, CO₂, sodium,potassium, calcium and intracellular fluid and the like. This can beachieved by probing the tissue with wavelengths of incident light 22 ibknown to be absorbed or cause fluorescence of these chromophores.Oxyhemoglobin has strong absorption bands in the visible spectrum withthe strongest absorption peak of occurring at 418 nm. Two additionalabsorption peaks with lower absorption coefficients occur at 542 and 577nm. Glucose is known to absorb in the near infrared range. Two othercancer predictive chromophores 33′ include NAD(P)H, and flavins thatfluoresce in the ultraviolet and near ultra-violet range.

[0071] Differences in the concentration of metabolites 33 for healthytissue verses metabolites for cancerous tissue 33′ result from themetabolic differences of cancerous tissue. A discussion will now bepresented of those differences. Since many cancer or tumors are overvascularized relative to normal tissue a higher total amount ofoxyhemoglobin in a given sample volume of tissue can indicate cancer. Atthe same time, since cancer cells are more rapidly dividing and havehigher metabolic rate than normal tissue the tumor will typically beslightly hypoxic and thus have lower PO₂ levels and or oxyhemoglobinconcentrations (or higher deoxyghemoglobin concentrations) relative tonormal tissue. Also, owing to higher metabolic rates, tumors willfrequently have lower interstitial glucose concentrations and higherPCO₂ levels as well as lower pH which sensor array 22 a can beconfigured to detect. Further, as described herein, tumors will havedifferent (usually higher) rates of DNA synthesis as well as abnormalDNA one or both of which can be detected by sensor array 22 a using DNAprobe methods.

[0072] In one embodiment of an optical biopsy method, fluorescencespectroscopy can be employed for optical biopsy including tissueidentification and ablation monitoring. In this method, the wavelength 7of the incident beam 22 ib is altered by interaction with the targettissue resulting in an emitted or returning light 22 rb at a differentwavelength known as the emitted wavelength 7 e. Sampling and analysis ofthe emitted light by detection member 22 md and coupled spectrometerdevice 17 (which in this embodiment is a UV spectrometer) results in thegeneration of a fluorescence emission spectrum 19 s. This is a plot ofthe intensity of emitted fluorescent light as a function of emissionwavelength produced when the target tissue is illuminated at aparticular wavelength 7 f Spectra 19 s is then compared matched to andto database 19 db of UV spectra for known cancer types or cancerpredictive metabolites 33′.

[0073] In other embodiments apparatus 10 and sensor array 22 a can beconfigured to detect and quantity metabolic chromophores or metabolites33 cn indicative of cell necrosis, injury or ablation. These metabolitesresult from various cellular functions occurring during cell necrosis.More specifically, when cells are heated by ablation treatment such asRF energy they heat to the point where their proteins are denatured,cell walls rupture and their contents released which includes a numberof necrotic indicating metabolites 33 cn. Such necrotic indicatingmetabolites 33 cn can include but are not limited to collagen, denaturedcollagen, fatty acids, lipids, cell membrane lipids, billirubin, andvapor bubbles and carbonized tissue. In a related embodiment, sensorarray 22 a can also be configured to monitor for decreases in metabolicchromophores 33 resulting from thermal or other ablative treatment. Forexample, decreases in hemoglobin due its thermal breakdown result in atissue color e.g. from red to white which can be readily detected bysensor array 22 a for portions or an entire target tissue site 5′.Besides hemoglobin, other decreasing chromophore 33 concentrations thatcan be monitored as indicators for cell necrosis include myoglohin,collagen and melanin.

[0074] In alternative embodiments, sensor array 22 a including members22 m, 22 me and 22 md can be configured to detect and distinguishbetween normal cells 6 and abnormal cells 6′ including abnormal cellshapes, sizes and morphology as a means of identifying cancerous,precancerous or other abnormal tissue. This can be accomplished using avariety of optical cell sorting and optical particle sizing techniquesknown in the art including fluorescence tagging methods. Cancer cells 6′will frequently be drastically different from a normal cell 6 includingbeing larger, having a larger more dense nucleus and being irregularlyshaped. Array 22 a can be configured to detect one or more of theseabnormalities and input them to logic resources 19. There modules 19 mcan be configured to compare these abnormalities to a database 19 db ofknown abnormalities and make a tissue identification based on patternrecognition or fuzzy logic algorithms which can be similar to those usedfor finger print identification.

[0075] In various embodiments apparatus 10 and sensor array 22 a can beconfigured to optically probe tissue site 5′ and generate an image ormap of the tumor volume and other structures within the target tissuesite 5′. In an embodiment shown in FIG. 13, apparatus 10 and sensorarray 20 a are configured to probe/scan the tissue volume 5″simultaneously in 3 dimensions (e.g. volumetrically sample) to determinethe border 5″b of tumor mass 5″ so as to locate and map the tumor mass5″ in 3 dimensions. The process can be facilitated by having one or moreknown reference points 5 r on members 18 that are determined via apositional sensor 22 p on deployment device 24″ that is configured todetermine deployment distance 43 of a selected member 18 e. (referencepoint 5 r can also be a radiopaque marker 11 positioned at set distancealong member 18 e). The mapping process can also be facilitated byrotating array 22 a about introducer axis 12 al or advancing andretracting one or more sensing members 22 m from members 18 or acombination of both. Signals 22 i from sensor array 22 a as well thosefrom position sensor 22 p can then be input to logic resources 19 lrwhere module 19 m generates a 3 dimensional map 4″ of the tumor volumeusing one or more image processing algorithms known in the artincluding, but not limited to, edge detection (to define tumor boundary5″B), filtering, volume imaging, contrast enhancement and fuzzy imageprocessing algorithms and the like. Module 19 m can then be configuredto display map 4″ on a coupled display device 21 (using volume imagedisplay algorithms such as numeric projection). The generation of 3D map4″ allows the user to accurately position energy delivery members 18 ewithin tumor mass 5″ while establishing the position of and avoidingnearby critical anatomical structures 5 cs. Further, the volumetricsampling and 3D mapping capability of embodiments of the inventionsolves the shortcomings of 2D intra-operative imaging methods includingpoor resolution of the tumor mass, difficulty in visualization of thetumor volume including misjudgment of the size, shape and location ofthe tumor volume. In related embodiments detectors 22 me can beconfigured to monitor in the near infrared range to produce aninfrared/thermal image 4 ir of sample volume 5 sv that can include tumormass 5″ or ablation volume 5 av.

[0076] In addition to identifying tissue types, apparatus 10 and sensorarrays 22 a can also be employed to monitor the progression of anablative procedure including the progression of an ablation volume 5 avresulting from the delivery of energy to target tissue volume 5.Referring now to FIGS. 14a and 14 b, emitters 22 a and detectors 22 mdcan be configured to monitor the moving boundary layer of cell necrosis55 and/or thermal fronts 55 t of a developing ablation volume 5 av. Thiscan be achieved by monitoring for the presence of metabolic chomophores33 or markers 9 indicative of cell necrosis or ablation describedherein. The spectral signal intensity 19 s (at one or more wave lengths7) for a volume of tissue between one or more emitters 22 me anddetector 22 md can be monitored over time. An endpoint for ablation canbe determined based on either a selectable threshold value 19 ts ofsignal 19 s or an inflection point or change in slope 19 ds (e.g. aderivative) of curve 19 s or a combination of both. In an embodimentsignal 19 s can comprise the subtraction of a baseline (or reference)spectral measurement 19 sbl of a nearby, but non-ablated tissue volume,from a real time measurement 19 srt of the target tissue volume duringthe time course of ablation. This compensates for any signal or tissuehysteresis over time. Signal/curve 19 s can include both spectral,thermal and impedance measurements. Values for 19 ts and 19 s can beinput and stored in logic resource 19 lr coupled to spectrophotometer 19or incorporated into an electronic algorithm controlling the delivery ofenergy which can be stored in a controller or processor 338 coupled topower supply 20.

[0077] In related embodiments, sensor array 22 a can be configured tomonitor for any number of indicators of cell necrosis that can beutilized to qualitatively or quantitatively assess the progress of anablation and determine a meaningful clinical endpoint. Such indicatorsand associated monitoring and endpoint methods include, but are notlimited to, the following: monitoring interstitial moisture or hydrationlevels (these would expect to go as cell lyse and then go down as fluidis boiled or evaporated) and utilizing a decrease below a lowerthreshold as an endpoint; monitoring interstitial electrolyteconcentrations (which increase with cell lysis); monitoring forinterstitial fatty acid and amino acid concentrations (which wouldincrease with cell lysis and then decrease due thermal degradation);monitoring for the increase or decrease of marker compounds 9;monitoring impedance; monitoring tissue temperature changes usingnear-infrared or thermocouple measurements; monitoring tissue colorchanges (e.g. red to white), monitoring for protein or collagendenaturization; monitoring for the release of DNA, gene fragments, DNAfragments or degraded DNA; monitoring for the release of RNA, RNAfragments or RNA fragments; monitoring for changes in tissue oxygenationin the form of PO₂ or oxyhemoglobin; monitoring for changes in PCO₂;monitor for decrease or cessation of blood flow rates (an indication oftissue coagulation) using optical (e.g. laser Doppler) or acoustical(e.g. doppler ultrasound) sensors and monitoring for the presence ofvapor bubbles and rate of vapor bubble formation. In a specificembodiment, sensor array is configured to monitor the rate of vaporbubble formation (using either optical and/or acoustic/ultrasoundsensors 22) and as an indicator of both rate of ablation and also atreatment endpoint. A treatment control and endpoint algorithm in module19 a employing this method would initially look for an increase inbubble rate formation and then a decrease below a set threshold as theendpoint. Other related embodiments can be configured to monitor forvarious cellular functions indicative of injury or necrosis.

[0078] The target tissue site 5″ can also be probed and interrogated bysensor array 22 a after the completion of ablation to confirm thatablation is complete for the entire desired volume ablation volume. Byprobing the ablated region with sensor array 22, the 3 dimensionalvolume of the ablation can be assessed and the margin 5 m of ablatedhealthy tissue beyond the tumor mass 5″ can also be measured.

[0079] Referring now to FIG. 15, in an embodiment power supply 20,display device 21, controller 329 and/or light source 17 and/or opticaldevice 19 can be incorporated or integrated into a single control anddisplay device or unit 20 cd. Device 20 cs can configured to includedisplay one or more of the following: spectral profile 19 s, tissue siteimage 4′, tumor volume image 4″, ablation volume image 4 av, timetemperature profiles, tissue identification information, and ablationsetting information (e.g. power setting, delivery time etc.). Device 20cd can also be configured to superimpose ablation volume image 4 av ontotumor volume image 4″ or tissue site image 4′ as well as superimposevisual cues 4 c on the placement (including proper and improperplacement) of apparatus 10 including energy delivery devices 18 e withinthe tumor volume 5″ or tissue site 5″. Device 20 cd can also includecontrols knobs 20 ck for manipulating any of the images (4′, 4″ or 4 av)in one or more axis.

[0080] Referring now to FIGS. 16a-16 c, in an embodiment of a method ofthe invention sensor array 22 a can be utilized to ensure properplacement of energy delivery member 18 e to achieve the desired ablationvolume 5 av as well as detect various improper placements. Referring toFIG. 16a, as energy delivery members 18 e are advanced out of introducer12 sensors 22 positioned at distal tip 18 de or sensor members 22/array22 a can be utilized to locate and map tumor mass 5″, sense the positionof energy delivery members 18 e relative to the tumor mass and determinean ablation volume 5 av based on the current position of members 18 e.As shown in FIG. 16a, sensors 22 or members 22 can be used to determineand alert the user when one or more energy delivery members arepositioned outside of tumor mass 5″ and/or when the resulting ablationvolume 5 av would not encompass the entire tumor mass 5″. Device 20 cdor other coupled monitoring device can then be configured to alert theuse of the necessity of repositioning one or more energy deliverymembers 18 e providing visual cues as to which member to move and by howmuch distance. Referring now to FIG. 16b, as members 18 e continue to beadvanced into the tumor volume mass sensors 22 or members 22 can alsodetermine if members 18 e not positioned properly to produce an ablationvolume 5 av that has an adequate healthy tissue margin 5 m with respectto tumor mass 5″. Again, the user could be alerted of the need toreposition one or more member 18 e. Referring now FIG. 16c, as members18 e continue to be advanced sensors 22 or member 22 can be configuredto determine when members 18 are properly positioned to produce thedesired ablation volume 5 av, the user being subsequently alerted bydevice 20 cd.

[0081] Referring now to FIGS. 17a and 17 b, in other method embodimentsof the invention sensors 20 or sensor array 22 a can be utilized todetect incomplete ablation volumes. In the embodiment shown in FIG. 17a,one or more members 18 e with coupled sensors 22 or sensor members 22 mcan be rotated about the introducer axis 12 to move the array members 22m from a first array position 22 a′ defining a first sample volume 5 sv1 to a second array position 22 a″ defining a second sample volume 5 sv2 so as to detect areas of incomplete ablation that are outside of theplane defined by two or more energy delivery members 18 e. By rotatingintroducer 12 or members 18, array 22 a can be rotated about axis 12 alin any desired amount from 1 to 360° to sample any desired tissue volumeand ascertain that the entire tumor volume 5″ has been ablated alongwith the desire amount of healthy tissue margin 5 m. In anotherembodiment shown in FIG. 17b, incomplete ablation can be determined byadvancing sensor members 22 m or passive members 18 with coupled sensors22 outside of the immediate area or volume 5 ev defined by energydelivery members 18 e and interrogating a desired tissue volume withsensors 22 or member 22 m to determine if it has been sufficientlyablated. This procedure can be repeated with sensor members 22 m ormember 18 being further advanced with subsequent tissue interrogationsuntil sensors members 22 m or sensors 22 are positioned at the border 5av′ of the desired ablation volume 5 av and a determination has beenmade that all sampled tissue has been adequately ablated.

[0082] Turning now to a further discussion of introducer 12, in variousembodiments, introducer 12 can be a trocar, catheter, multi-lumencatheter, or a wire-reinforced or metal-braided polymer shaft, a portdevice, a subcutaneous port device or other medical introducing deviceknown to those skilled in the art. In various embodiments, introducer 12as well as resilient member 18 can be configured to have varyingmechanical properties along their respective lengths including, but notlimited to variable stiffness, torquability, bendability, flexuralmodulus, pushability, trackability and other mechanical performanceparameters known in the catheter arts. Referring to FIG. 18a, this canbe achieved through the use of stiff shafts sections 12′″ disposedwithin portions of introducer 12 along its length 12″. It can also beaccomplished through the use of braids, varying/tapered diameters anddifferent materials (e.g. stiffer materials joined to flexiblematerials) positioned over portions of introducer 12. Sections 12′″ madefrom different materials can be joined using introducer bonding methodsknown in the art such as hot melt junctions (with and without capturetubes/collates), adhesive joints, but joints and the like. The joiningmethod can be controlled/selected so as to control the mechanicaltransition 12 mt between two sections to a desired gradient (e.g. smoothvs. abrupt). In related embodiments, introducer 12 and/or member 18 canbe configured to have stiffer proximal portions and more flexible distalportions so as to facilitate one or more of the following (i) introducersteerability and positioning of distal tip 16 at a selectable targettissue site 5′, (ii) reduced risk of perforation, abrasion and othertrauma during the positioning the introducer to the tissue site. Invarious embodiments, the transition from the stiffer to the moreflexible portion can be configured to be either (i) gradual with alinear or curve-linear transition, (ii) a step or abrupt transition, and(iii) combinations thereof.

[0083] Referring to FIGS. 18b and 18 c, introducer 12 can have asubstantially circular, semicircular, oval or crescent shaped crosssectional profile 12 cs, as well as combinations thereof along itslength. Similarly, lumens 13 can have a circular, semicircular, oval orcrescent shaped cross section for all or a portion of the 12′ length ofintroducer 12.

[0084] Suitable materials for introducer 12 and resilient member 18include, but are not limited to, stainless steel, shape memory alloyssuch as nickel titanium alloys, polyesters, polyethylenes,polyurethanes, Pebax®, polyimides, nylons, copolymers thereof and othermedical plastics known to those skilled in the art. All or portions ofintroducer 12 can be coated with a lubricious coating or film 12′ whichreduces the friction (and hence trauma) of introducer 12 with hepatic,pulmonary, bone and other tissue. Such coatings can include but are notlimited to silicones, PTFE (including Teflon®) and other coatings knownin the art. In a related embodiment introducer 12 and member 18 can havean optical coating 37 on their exterior surface or within lumens 13 or72 that is configured to reduce reflection or glare from theirrespective surfaces that may cause false optical signals or otherwiseinterfere with the optical sampling process by sensing members 22.Optical coating 37 can be any non-reflective, glare resistant coatingknown in the art or can be a surface treatment such as anodization.

[0085] Also, all or portions of apparatus 10 including introducer 12 andmembers 18 can be constructed of materials known in the art that areoptimized and/or compatible with radiation sterilizations (e.g. Gamma orE-beam). In related embodiments, all or portions of apparatus 10 can beconfigured (e.g. lumen diameter to length ratio, etc) to be sterilizedby plasma (e.g. H₂O₂) sterilization by systems.

[0086] Referring now to FIG. 20, in other embodiments all or portions ofintroducer 12 or resilient members 18 can be configured to bedeflectable and/or steerable using deflection mechanisms 25 which caninclude pull wires 15, ratchets, cams, latch and lock mechanisms,piezoelectric materials and other deflection means known in the art. Theamount of deflection of introducer 12 is selectable and can beconfigured to allow the maneuvering of introducer 12 through tortuousvasculator and other anatomy. In specific embodiments, the distalportions of introducer 12 can be configured to deflect 0-180° or more inup to three axes to allow the tip of introducer 12 to have retrogradepositioning capability. Deflection mechanism 25 can be coupled to orintegral with a moveable or slidable actuator 24″, 25′ on handpiece 24.Mechanism 25 and coupled actuator 25′ are configured to allow thephysician to selectively control the amount of deflection 25 of distaltip 16 or other portion of introducer 12. Actuator 25′ can be configuredto both rotate and deflect distal tip 16 by a combination of rotationand longitudinal movement of the actuator.

[0087] Referring now to FIG. 20, in various embodiments introducer 12can be coupled at its proximal end 14 to a handle 24 or handpiece 24.Handpiece 24 can be detachable and can include ports 24′ and actuators24″. Ports 24′ can be coupled to one or more lumens 13 (and in turnlumens 72) and can include fluid and gas ports/connectors andelectrical, optical connectors. In various embodiments, ports 24′ can beconfigured for aspiration (including the aspiration of tissue), and thedelivery of cooling, electrolytic, irrigation, polymer and other fluids(both liquid and gas) described herein. Ports 24′ can include but arenot limited to luer fittings, valves (one-way, two-way), toughy-bourstconnectors, swage fittings and other adaptors and medical fittings knownin the art. Ports 24′ can also include lemo-connectors, computerconnectors (serial, parallel, DIN, etc) micro connectors and otherelectrical varieties well known to those skilled in the art. Further,ports 24′ can include opto-electronic connections which allow opticaland electronic coupling of optical fibers and/or viewing scopes toilluminating sources, eye pieces, video monitors and the like. Actuators24″ can include rocker switches, pivot bars, buttons, knobs, ratchets,levers, slides and other mechanical actuators known in the art, all orportion of which can be indexed. These actuators can be configured to bemechanically, electro-mechanically, or optically coupled to pull wires,deflection mechanisms and the like allowing selective control andsteering of introducer 12. Handpiece 24 can be coupled to tissueaspiration/collection devices 26, fluid delivery devices 28 (e.g.infusion pumps) fluid reservoirs (cooling, electrolytic, irrigation etc)30 or power source 20 through the use of ports 24′. Tissueaspiration/collection devices 26 can include syringes, vacuum sourcescoupled to a filter or collection chamber/bag. Fluid delivery device 28can include medical infusion pumps, Harvard pumps, syringes and thelike. In specific embodiments, aspiration device 26 can be configuredfor performing thoracentesis which is a procedure for removing pleuralfluid percutaneously.

[0088] Turning now to a discussion of resilient members 18, thesemembers can be of different sizes, shapes and configurations withvarious mechanical properties selected for the particular tissue site.In one embodiment, members 18 can be needles, with sizes in the range of28 to 12 gauge with specific embodiments of 14, 16 and 18 gauges.Resilient members 18 are configured to be in non-deployed positionswhile retained in introducer 12. In the non-deployed positions,resilient members 18 may be in a compacted state, spring loaded,generally confined or substantially straight if made of a suitablememory metal such as nitinol. As resilient members 18 are advanced outof introducer 12 they become distended to a deployed state, whichcollectively defines an ablative volume 5 av, from which tissue isablated as illustrated more fully in FIGS. 1, 2, 19 and 16 a-16 c. Theselectable deployment of resilient members 18 can be achieved throughone or more of the following approaches (i) the amount of advancement ofresilient members 18 from introducer 12; (ii) independent advancement ofresilient members 18 from introducer 12; (iii) the lengths and/or sizesof energy delivery surfaces of electrodes 18 and 18′; (iv) variation inmaterials used for electrode 18; and (v) variation of the geometricconfiguration of electrode 18 in their deployed states.

[0089] As described herein, in various embodiments all or a portion ofresilient member 18 can be an energy delivery device or member 18 e.Turning to a discussion of energy delivery device and power sources, thespecific energy delivery devices 18 e and power sources 20 that can beemployed in one or more embodiments of the invention include but are notlimited to, the following: (i) a microwave power source coupled to amicrowave antenna providing microwave energy in the frequency range fromabout 915 MHz to about 2.45 GHz (ii) a radio-frequency (RF) power sourcecoupled to an RF electrode, (iii) a coherent light source coupled to anoptical fiber or light pipe, (iv) an incoherent light source coupled toan optical fiber, (v) a heated fluid coupled to a catheter with a closedor at least partially open lumen configured to receive the heated fluid,(vi) a cooled fluid coupled to a catheter with a closed or at leastpartially open lumen configured to receive the cooled fluid (viii) acryogenic fluid, (ix) a resistive heating source coupled to a conductivewire, (x) an ultrasound power source coupled to an ultrasound emitter,wherein the ultrasound power source produces ultrasound energy in therange of about 300 KHZ to about 3 GHz, (xi) and combinations thereof.For ease of discussion for the remainder of this application, the energydelivery device 118 e is one or more RF electrodes 18 e and the powersource utilized is an RF power supply. For these and relatedembodiments, RF power 20 supply can be configured to deliver 5 to 200watts, preferably 5 to 100, and still more preferably 5 to 50 watts ofelectromagnetic energy is to the electrodes of energy delivery device 18without impeding out. The electrodes 118 e are electromagneticallycoupled to energy source 20. The coupling can be direct from energysource 20 to each electrode 18 e respectively, or indirect by using acollet, sleeve and the like which couples one or more electrodes toenergy source 20.

[0090] In various embodiments, electrodes 18 e can have a variety ofshapes and geometries. Referring now to FIGS. 21a-21 f, example shapesand geometries can include, but are not limited to, ring-like, ball,hemispherical, cylindrical, conical, needle-like and combinationsthereof.

[0091] Referring to FIG. 22, in an embodiment electrode 18 e can be aneedle with sufficient sharpness to penetrate tissue including fibroustissue including, encapsulated tumors cartilage and bone. The distal end18 de of electrode 18 e can have a cut angle 68 that ranges from 1 to60°, with preferred ranges of at least 25° or, at least 30° and specificembodiment of 25° and 30°. The surface of electrode 18 e can be smoothor textured and concave or convex. Electrode 18 e can have differentlengths 38 that are advanced from distal end 16′ of introducer 12. Thelengths can be determined by the actual physical length of electrode(s)18 e, the length 38′ of an energy delivery surface 18 eds of electrode18 e and the length, 38″ of electrode 18 e that is covered by aninsulator 36. Suitable lengths 38 include but are not limited to a rangefrom 1-30 cms with specific embodiments of 0.5, 1, 3, 5, 10, 15 and 25.0cm. The conductive surface area 18 eds of electrode 18 e can range from0.05 mm2 to 100 cm2. The actual lengths of electrode 18 e depend on thelocation of tissue site 5′ to be ablated, its distance from the site,its accessibility as well as whether or not the physician performs anendoscopic or surgical procedure. While the conductive surface area 18eds depends on the desired ablation volume 5 av to be created.

[0092] Referring now to FIGS. 23 and 24, electrode 18 e can also beconfigured to be flexible and or deflectable having one or more radii ofcurvature 70 which can exceed 180° of curvature. In use, electrode 18 ecan be positioned to heat, necrose or ablate any selected target tissuevolume 5′. A radiopaque marker 11 can be coated on electrodes 18 e forvisualization purposes. Electrode 18 e can be coupled to introducer 12and or an advancement member or device 15 or and advancement-retractionmember 34 using soldering, brazing, welding, crimping, adhesive bondingand other joining methods known in the medical device arts. Also,electrode 18 e can include one or more coupled sensors 22 to measuretemperature and impedance (both of the electrode and surroundingtissue), voltage and current other physical properties of the electrodeand adjacent tissue. Sensors 22 can be at exterior surfaces ofelectrodes 18 e at their distal ends or intermediate sections.

[0093] Electrode 18 e can be made of a variety of conductive materials,both metallic and non-metallic. Suitable materials for electrode 18 einclude, steel such as 304 stainless steel of hypodermic quality,platinum, gold, silver and alloys and combinations thereof. Also,electrode 18 e can be made of conductive solid or hollow straight wiresof various shapes such as round, flat, triangular, rectangular,hexagonal, elliptical and the like. In a specific embodiment all orportions of electrodes 18 e or a second electrode 18 e′ can be made of ashaped memory metal, such as NiTi, commercially available from RaychemCorporation, Menlo Park, Calif.

[0094] Referring now to FIGS. 25 through 28 in various embodiments oneor more electrodes 18 e can be covered by an insulative layer 36 so asto have an exterior surface that is wholly or partially insulated andprovide a non-insulated area which is an energy delivery surface 18 eds.In an embodiment shown in FIG. 25, insulative layer 36 can comprise asleeve that can be fixed or slidably positioned along the length ofelectrode 18 e to vary and control the length 36′ of energy deliverysurface 18 eds. Suitable material for insulative layer 36 includepolyimide and flouro-carbon polymers such as TEFLON.

[0095] In the embodiment shown in FIG. 26, insulation 36 is formed atthe exterior of electrodes 18 e in circumferential patterns, leaving aplurality of energy delivery surfaces 18 eds. In an embodiment shown inFIGS. 27 and 28, insulation 36 extends along a longitudinal exteriorsurface of electrodes 18 e. Insulation 36 can extend along a selecteddistance along a longitudinal length of electrodes 18 e and around aselectable portion of a circumference of electrodes 18 e. In variousembodiments, sections of electrodes 18 e can have insulation 36 alongselected longitudinal lengths of electrodes 18 e as well as completelysurround one or more circumferential sections of electrodes 18 e.Insulation 36 positioned at the exterior of electrodes 18 e can bevaried to define any desired shape, size and geometry of energy deliverysurface 18 eds.

[0096] Referring now to FIG. 29, in various embodiments electrode 18 ecan include one or more lumens 72 (which can be contiguous with or thesame as lumen 13) coupled to a plurality of fluid distribution ports 23(which can be apertures 23) from which a variety of fluids 27 can beintroduced, including conductivity enhancing fluids, electrolyticsolutions, saline solutions, cooling fluids, cryogenic fluids, gases,chemotherapeutic agents, medicaments, gene therapy agents,photo-therapeutic agents, contrast agents, infusion media andcombinations thereof. This is accomplished by having ports or apertures23 that are fluidically coupled to one or more lumens 72 coupled tolumens 13 in turn coupled to fluid reservoir 30 and/or fluid deliverydevice 28.

[0097] In an embodiment shown in FIG. 29, a conductivity enhancingsolution 27 can be infused into target tissue site 5′ including tissuemass 5″ The conductivity enhancing solution can be infused before duringor after the delivery of energy to the tissue site by the energydelivery device. The infusion of a conductivity enhancing solution 27into the target tissue 5′ creates an infused tissue area 5 i that has anincreased electrical conductivity (verses un-infused tissue) so as toact as an enhanced electrode 40. During RF energy delivery, the currentdensities in enhanced electrode 40 are greatly lowered allowing thedelivery of greater amounts of RF power into electrode 40 and targettissue 5′ without impedance failures. In use, the infusion of the targettissue site with conductivity enhancing solution provides two importantbenefits: (i) faster ablation times; and (ii) the creation of largerlesions; both without impedance-related shut downs of the RF powersupply. This is due to the fact that the conductivity enhancing solutionreduces current densities and prevents desiccation of tissue adjacentthe electrode that would otherwise result in increases in tissueimpedance. A preferred example of a conductivity enhancing solution is ahypertonic saline solution. Other examples include halide saltsolutions, and colloidal-ferro solutions and colloidal-silver solutions.The conductivity of enhanced electrode 40 can be increased by control ofthe rate and amount of infusion and the use of solutions with greaterconcentrations of electrolytes (e.g. saline) and hence greaterconductivity. In various embodiments, the use of conductivity enhancingsolution 27 allows the delivery of up to 2000 watts of power into thetissue site impedance shut down, with specific embodiments of 50, 100,150, 250, 500, 1000 and 1500 watts achieved by varying the flow, amountand concentration of infusion solution 27. The infusion of solution 27can be continuous, pulsed or combinations thereof and can be controlledby a feedback control system described herein. In a specific embodimenta bolus of infusion solution 27 is delivered prior to energy deliveryfollowed by a continuous delivery initiated before or during energydelivery with energy delivery device 18 e or other means.

[0098] Turning to a discussion of sensors, the use of one or moresensors 22 coupled to the introducer, energy delivery devices,deployable member and biopsy needles and permits accurate measurement oftemperature at tissue site 5′ in order to determine, (i) the extent ofcell necrosis, (ii) the amount of cell necrosis, (iii) whether or notfurther cell necrosis is needed and (iv) the boundary or periphery ofthe ablated tissue mass. Further, sensor 22 reduces non-targeted tissuefrom being injured, destroyed or ablated. Referring to FIG. 24, multiplesensors can be coupled to electrodes 18.

[0099] Sensor 22 can be selected to measure temperature, tissueimpedance or other tissue property described herein to permit real timemonitoring of energy delivery. This reduces damage to tissue surroundingthe targeted mass to be ablated. By monitoring the temperature atvarious points within and outside of the interior of tissue site 5′, adetermination of the selected tissue mass periphery can be made, as wellas a determination of when cell necrosis is complete. If at any timesensor 22 determines that a desired cell necrosis temperature isexceeded, then an appropriate feedback signal is received at an energysource 20 coupled to energy delivery device 18 which then regulates theamount of electromagnetic energy delivered to electrodes 18 and 18′.

[0100] Turning now to a discussion of sensors, sensor 22 can be ofconventional design, including but not limited to thermal sensors,acoutiscal sensors, optical sensors, pH sensors, gas sensors, flowsensors positional sensors and pressure/force sensors. Thermal sensorscan include thermistors, thermocouples, resistive wires, optical sensorsand the like. A suitable thermal sensor 22 includes a T typethermocouple with copper constantene, J type, E type, K type, fiberoptics, resistive wires, thermocouple IR detectors, and the like.Acoustical sensors can include ultrasound sensors includingpiezoelectric sensors which can be configured in an array. Pressure andforce sensors can include strain gauge sensors including silicon-basedstrain gauges. Optical sensors can include photomultipliers, opticaldiodes, fiber optics, and micro-machined optical fibers. Gas sensors caninclude O2 sensors such as Clark electrodes, CO2 sensors and otherelectrochemical based sensors known in the art. Flow/velocity sensorscan include ultrasound sensors, electromagnetic sensors and aneometricsensors which can be configured to detect both liquid and gaseous flows.Positional sensors can include LVDT's, and Hall effect sensors. Othersensors which can be employed in various embodiments of the invention,include impedance sensors, antibody-based sensors, electrochemicalbiosensors, (e.g. glucose), gene chips, silicon-based gene chips,oglionucleotide-based gene chip sensors, and chemical sensors. Invarious embodiments, one sensor can be configured to detect multipleparameters or one or more sensors can be coupled together to deliverinput on multiple parameters which can be multiplexed to an input deviceto a controller or microprocessor. Pressure sensors can be selectedand/or configured to detect pressure differentials less than 1 mmHg andeven less than 0.1 mmHg. In specific embodiments, pressure sensor 22 canbe a micro-machined fiber optic sensor, a PSP-1 pressure sensors madeGaymar Industries Inc., (Orchard Park N.Y.) or a Monolithic IntegratedPressure sensor made by the Fraunhofer-Institut (Duisburg, Germany).Also, ultrasound sensor or transducers can be a Model 21362 imagingprobe by the Hewlett Packard Company, Palo Alto, Calif.

[0101] In various embodiments, analytical genetic methods including DNAprobe methods and techniques can be utilized to monitor rates of DNAsynthesis for target tissue 5′ and a comparison can be made betweenrates of synthesis to determine cancerous versus healthy tissue. In anembodiment, sensor array 22 a can be configured to detect such rates ofDNA synthesis and logic resources 19 lr or control system 329 canconfigured with algorithms to measure and determine threshold ratios ofDNA synthesis as an predictor of cancerous tissue. The ratio can varyfor different types of tissue (e.g. hepatic, gastro-mucosal prostate,mucosal, submucosal etc.) and different types of cancer. Specific DNAsynthesis ratios (healthy vs. target tissue) indicative of cancer caninclude, but are not limited to: 1:1.1, 1:1.3, 1:1.5, 1:2. 1:3, 1:5,1:10, 1:20, 1:50 and 1:100.

[0102] An alternative embodiment of an in vivo tumor biopsy methodutilizes a radiolabel marker compound bound to a tumor specific primaryantibody that is detected by a radiation detection device (not shown)coupled to sensing member 22 and/or resilient member 18 and also coupledto optical detection device 19. Given the target tissue organ, priordiagnostic imaging diagnosis the physician could select among severalantibodies that are likely matches to the suspected tumor. Oralternatively, he or she could start off with an antibody to many commontumors and then utilizes ones with increasing specificity as means tonarrow down the tumor type. Also, a secondary label can be used as asubtraction agent to enhance sensitivity. The radiation detection devicecan be configured to detect alpha, gamma, beta, positron or otherradioactive particle. Preferably, the label used is positron and/or hasan extremely short half life (e.g. hours). The detector device can beconfigured to discriminate between different energies of incidentradiation, e.g., between gamma radiation in different ranges within thebroad 50-500 KeV range which is normally used for gamma scintillationcounters and/or between alpha, gamma and beta radiation emitted bylabels on the specific and a second or different antibody. Further, thedetector can be configured to distinguish between the radiation emittedby the primary antibody label and that emitted by a subtraction agent,in those cases where dual antibody correction is used to enhancesensitivity. This can be achieved by embodiments having two differentdetector devices or by using a single detector configured to recordcounts of different energies in different channels, or to distinguish byother electronic means between radiation of different types or energies.In another embodiment this can be achieved by configuring coupledoptical measurement device 17 with photomultiplier and comparatorcircuitry that detects differences in brightness of a scintillationcrystal response that correlate to differences in photon energy ofincident gamma radiation. The circuit can be configured to respond onlyto energy levels above a selected level corresponding to the desiredgamma energy band for one of the two radioisotopes.

[0103] In an embodiment, the radiation detector can be a scintillationcrystal optically mounted on the end of a fiber optic sensing member 22,that is configured to transmit the optical response of the crystal toincident gamma radiation to a photomultiplier and associated detectioncircuitry which comprise are integral or otherwise comprise opticalmeasurement device 19. This configuration reduces the size of thedetector to be compatible with a percutaneous introducing device, suchas a catheter or trocar. The introducing device can be shielded to serveas a collimator, where necessary, and/or fitted with a window at a knowndistance from its terminus, with the scintillation crystal internallyhoused.

[0104] In preferred embodiments, the radionuclide label used for tumordetection is an isotope with a gamma radiation emission peak in therange of 50-500 Kev. Suitable radionuclides include but are not limitedto e.g., Iodine-131, Iodine-123, Iodine-126, Iodine-133, Bromine-77,Indium-111, Indium-113 m, Copper-67, Gallium-67, Gallium-68,Ruthenium-95, Ruthenium-97, Ruthenium-103, Ruthenium-105, Mercury-197,Mercury-203, Rhodium-99 m, Rhodium-101, Rhodium-105, Tellurium-121 m,Tellurium-122 m, Tellurium-125 m, Thulium-165, Thulium-167, Thulium-168,Rhenium-186, Technetium-99 m Fluorine-18. In embodiments utilizingmultiple isotopes for method utilizing dual isotope correction, the twolabels selected can be of sufficiently different energies to beseparately detectable with the same radiation probe. Suitable such pairsof radioisotopes include, e.g., Iodine-131/Iodine 123,Gallium-67/Indium-111, Iodine-131/Technetium-99 m and the like.Preferably, the paired radionuclides used for subtraction do not bothhave significant scatter into the channels where the emission of theother nuclide is being detected. One-way scatter can readily becorrected for by filtering algorithms known in the art.

[0105] Referring now to FIGS. 30 and 31, a feedback control system 329can be connected to energy source 320, sensors 324 and energy deliverydevices 314 and 316. Feedback control system 329 receives temperature orimpedance data from sensors 324 and the amount of electromagnetic energyreceived by energy delivery devices 314 and 316 is modified from aninitial setting of ablation energy output, ablation time, temperaturesand current density (the “Four Parameters”). Feedback control system 329can automatically change any of the Four Parameters. Feedback controlsystem 329 can detect impedance or temperature and change any of theFour Parameters. Feedback control system 329 can include a multiplexer(digital or analog) to multiplex different electrodes, sensors, sensorarrays and a temperature detection circuit that provides a controlsignal representative of temperature or impedance detected at one ormore sensors 324. A microprocessor can be connected to the temperaturecontrol circuit.

[0106] The following discussion pertains particularly to the use of anRF energy source with an optical biopsy treatment apparatus 10. Forpurposes of this discussion, energy delivery devices 314 and 316 willnow be referred to as RF electrodes/antennas 314 and 316 and energysource 320 will now be an RF energy source. However it will beappreciated that all other energy delivery devices and sources discussedherein are equally applicable and devices similar to those associatedwith biopsy treatment apparatus 10 can be utilized with laser opticalfibers, microwave devices and the like. The temperature of the tissue,or of RF electrodes 314 and 316 is monitored, and the output power ofenergy source 320 adjusted accordingly. The physician can, if desired,override the closed or open loop system.

[0107] The user of apparatus 10 can input an impedance value thatcorresponds to a setting position located at apparatus 10. Based on thisvalue, along with measured impedance values, feedback control system 329determines an optimal power and time needed in the delivery of RFenergy. Temperature is also sensed for monitoring and feedback purposes.Temperature can be maintained to a certain level by having feedbackcontrol system 329 adjust the power output automatically to maintainthat level.

[0108] In another embodiment, feedback control system 329 determines anoptimal power and time for a baseline setting. Ablation volumes orlesions are formed at the baseline first. Larger lesions can be obtainedby extending the time of ablation after a center core is formed at thebaseline. The completion of lesion creation can be checked by advancingenergy delivery device 316 from distal end 16′ of introducer 12 to aposition corresponding to a desired lesion size and monitoring thetemperature at the periphery of the lesion such that a temperaturesufficient to produce a lesion is attained.

[0109] The closed loop system 329 can also utilize a controller 338 tomonitor the temperature, adjust the RF power, analyze the result, refeedthe result, and then modulate the power. More specifically, controller338 governs the power levels, cycles, and duration that the RF energy isdistributed to electrodes 314 and 316 to achieve and maintain powerlevels appropriate to achieve the desired treatment objectives andclinical endpoints. Controller 338 can also in tandem analyze spectralprofile 19 s and perform tissue biopsy identification and ablationmonitoring functions including endpoint determination. Further,controller 338 can in tandem govern the delivery of electrolytic,cooling fluid and, the removal of aspirated tissue. Controller 338 canbe integral to or otherwise coupled to power source 320. In this andrelated embodiments, controller 338 can be coupled to light source 317and can be configured to synchronize the delivery of pulsed power totissue site to allow for sensing by sensors or sensor array 322 a duringoff power off intervals to prevent or minimize signal interference,artifacts or unwanted tissue effects during sampling by sensors 324 orsensor array 322 a. The controller 338 can also be coupled to aninput/output (I/O) device such as a keyboard, touchpad, PDA, microphone(coupled to speech recognition software resident in controller 338 orother computer) and the like.

[0110] Referring now to FIG. 30, all or portions of feedback controlsystem 329 are illustrated. Current delivered through RF electrodes 314and 316 (also called primary and secondary RF electrodes/antennas 314and 316) is measured by a current sensor 330. Voltage is measured byvoltage sensor 332. Impedance and power are then calculated at power andimpedance calculation device 334. These values can then be displayed ata user interface and display 336. Signals representative of power andimpedance values are received by controller 338 which can be amicroprocessor 338.

[0111] A control signal is generated by controller 338 that isproportional to the difference between an actual measured value, and adesired value. The control signal is used by power circuits 340 toadjust the power output in an appropriate amount in order to maintainthe desired power delivered at the respective primary and/or secondaryantennas 314 and 316. In a similar manner, temperatures detected atsensors 324 provide feedback for maintaining a selected power. Theactual temperatures are measured at temperature measurement device 342,and the temperatures are displayed at user interface and display 336. Acontrol signal is generated by controller 338 that is proportional tothe difference between an actual measured temperature, and a desiredtemperature. The control signal is used by power circuits 340 to adjustthe power output in an appropriate amount in order to maintain thedesired temperature delivered at the respective sensor 324. Amultiplexer 346 can be included to measure current, voltage andtemperature, at the numerous sensors 324 as well as deliver anddistribute energy between primary electrodes 314 and secondaryelectrodes 316.

[0112] Controller 338 can be a digital or analog controller, or acomputer with embedded, resident or otherwise coupled software. In anembodiment controller 338 can be a Pentium® family microprocessormanufacture by the Intel® Corporation (Santa Clara, Calif.). Whencontroller 338 is a computer it can include a CPU coupled through asystem bus. On this system can be a keyboard, a disk drive, or othernon-volatile memory systems, a display, and other peripherals, as areknown in the art. Also coupled to the bus are a program memory and adata memory. In various embodiments controller 338 can be coupled toimaging systems, including but not limited to ultrasound, CT scanners(including fast CT scanners such as those manufacture by the ImatronCorporation (South San Francisco, Calif.), X-ray, MRI, mammographicX-ray and the like. Further, direct visualization and tactile imagingcan be utilized.

[0113] User interface and display 336 can include operator controls anda display. In an embodiment user interface 336 can be a PDA device knownin the art such as a Palm® family computer manufactured by Palm®)Computing (Santa Clara, Calif.). Interface 336 can be configured toallow the user to input control and processing variables, to enable thecontroller to generate appropriate command signals. Interface 336 canalso receives real time processing feedback information from one or moresensors 324 for processing by controller 338, to govern the delivery anddistribution of energy, fluid etc.

[0114] The output of current sensor 330 and voltage sensor 332 is usedby controller 338 to maintain a selected power level at primary andsecondary antennas 314 and 316. The amount of RF energy deliveredcontrols the amount of power. A profile of power delivered can beincorporated in controller 338, and a preset amount of energy to bedelivered can also be profiled.

[0115] Circuitry, software and feedback to controller 338 results inprocess control, and the maintenance of the selected power, and are usedto change, (i) the selected power, including RF, microwave, laser andthe like, (ii) the duty cycle (on-off and wattage), (iii) bipolar ormonopolar energy delivery and (iv) infusion medium delivery, includingflow rate and pressure. These process variables are controlled andvaried, while maintaining the desired delivery of power independent ofchanges in voltage or current, based on temperatures monitored atsensors 324. A controller 338 can be incorporated into feedback controlsystem 329 to switch power on and off, as well as modulate the power.Also, with the use of sensor 324 and feedback control system 329, tissueadjacent to RF electrodes 314 and 316 can be maintained at a desiredtemperature for a selected period of time without causing a shut down ofthe power circuit to electrode 314 due to the development of excessiveelectrical impedance at electrode 314 or adjacent tissue.

[0116] Referring now to FIG. 31, current sensor 330 and voltage sensor332 are connected to the input of an analog amplifier 344. Analogamplifier 344 can be a conventional differential amplifier circuit foruse with sensors 324. The output of analog amplifier 344 is sequentiallyconnected by an analog multiplexer 346 to the input of A/D converter348. The output of analog amplifier 344 is a voltage which representsthe respective sensed temperatures. Digitized amplifier output voltagesare supplied by A/D converter 348 to a microprocessor 350.Microprocessor 350 may be a Power PC® chip available from Motorola or anIntel® Pentium® Series chip. However, it will be appreciated that anysuitable microprocessor or general purpose digital or analog computercan be used to calculate impedance or temperature or perform imageprocessing and tissue identification functions.

[0117] Microprocessor 350 sequentially receives and stores digitalrepresentations of impedance and temperature. Each digital valuereceived by microprocessor 350 corresponds to different temperatures andimpedances. Calculated power and impedance values can be indicated onuser interface and display 336. Alternatively, or in addition to thenumerical indication of power or impedance, calculated impedance andpower values can be compared by microprocessor 350 with power andimpedance limits. When the values exceed predetermined power orimpedance values, a warning can be given on user interface and display336, and additionally, the delivery of RF energy can be reduced,modified or interrupted. A control signal from microprocessor 350 canmodify the power level supplied by energy source 320 to RF electrodes314 and 316. In a similar manner, temperatures detected at sensors 324provide feedback for determining the extent and rate of (i) tissuehyperthermia (ii) cell necrosis; and (iii) when a boundary of desiredcell necrosis has reached the physical location of sensors 324.

[0118] Conclusion:

[0119] It will be appreciated that the applicants have provided a noveland useful apparatus and method for the biopsy and treatment of tumorsusing minimally invasive methods. The foregoing description of apreferred embodiment of the invention has been presented for purposes ofillustration and description. It is not intended to be exhaustive or tolimit the invention to the precise forms disclosed. Embodiments of theinvention can be configured for the biopsy and treatment of tumor andtissue masses in a number of organs including but no limited to theliver, breast, bone and lung. However, embodiments of the invention areapplicable to other organs and tissue as well. Obviously, manymodifications and variations will be apparent to practitioners skilledin this art. Further, elements from one embodiment can be readilyrecombined with elements from one or more other embodiments. Suchcombinations can form a number of embodiments within the scope of theinvention. It is intended that the scope of the invention be defined bythe following claims and their equivalents.

What is claimed is:
 1. A method of treating a tumor comprising:providing a tissue biopsy and treatment apparatus for detecting andtreating a tumor, the apparatus comprising an elongated delivery deviceincluding a lumen, the elongated delivery device being maneuverable intissue; a sensor array deployable from the elongated member, the sensorarray including a plurality of resilient members, at least one of theplurality of resilient members being positionable in the elongateddelivery device in a compacted state and deployable with curvature intotissue from the elongated delivery device in a deployed state, at leastone of the plurality of resilient members including at least one of asensor, a tissue piercing distal end or a lumen, the sensor array havinga geometric configuration adapted to volumetrically sample tissue at atissue site to differentiate or identify tissue at the tissue site; andat least one energy delivery device coupled to one of the sensor array,at least one of the plurality of resilient members or the elongateddelivery device; introducing the apparatus into a target tissue site;distinguishing a tissue type utilizing the sensor array; positioning theenergy delivery device utilizing tissue type information derived fromthe sensor array to ablate a tumor volume; delivering energy from theenergy delivery device to ablate or necrose at least a portion of thetumor volume; and determining an amount of tumor volume ablationutilizing the sensor array.
 2. The method of claim 1, furthercomprising: monitoring a tissue volume in the target tissue site.
 3. Themethod of claim 2, wherein the apparatus includes logic resourcescoupled to at least one of the sensor, the energy delivery device or apower source coupled to the energy delivery device, the method furthercomprising: adjusting one of a power, current, power duty cycle or fluidflow response to an input from the sensor array.
 4. The method of claim3, wherein the input is at least one of a temperature, an impedance, anoptical absorbance, an optical reflectance or a pH.
 5. The method ofclaim 3, wherein the logic resources include at least one of aprocessor, a microprocessor, a software module, a fizzy logic module, atemperature compensation module, or a database.
 6. The method of claim2, wherein the tissue volume includes at least a first tissue volume anda second tissue volume.
 7. The method of claim 6, wherein the at least afirst tissue volume is in closer proximity to the energy delivery devicethan the second tissue volume.
 8. The method of claim 6, wherein thefirst tissue volume is within a tumor volume and the second tissuevolume is outside of the tumor volume.
 9. The method of claim 1, furthercomprising: comparing a first tissue volume to a second tissue volume.10. The method of claim 9, wherein the first tissue volume is insubstantial proximity to a first portion of the sensor array and thesecond tissue volume is in substantial proximity to a second portion ofthe sensor array.
 11. The method of claim 10, further comprising:positioning the first portion of the sensor array in the first tissuevolume and the second portion of the sensor array in the second tissuevolume.
 12. The method of claim 9, further comprising: comparing aproperty of the first tissue volume to a property of the second tissuevolume.
 13. The method of claim 13, wherein the tissue property includesat least one of a physiologic property, a metabolic property, a geneticproperty, a thermal property, a temperature, an electrical property, animpedance, an optical property, an absorbance, a reflectance, adimensional property or a pH.
 14. The method of claim 9, wherein thefirst tissue volume is within a tumor volume and the second tissuevolume is outside of the tumor volume.
 15. The method of claim 9,further comprising differentiating between a first tissue type in thefirst tissue volume and a second tissue type in the second tissuevolume.
 16. The method of claim 10, wherein at least the first sensorarray portion is positioned in closer proximity to the energy deliverydevice than the second sensor array portion.
 17. The method of claim 10,wherein at least the first sensor array portion includes a firstplurality of sensors and the second sensor array portion includes asecond plurality of sensors.
 18. The method of claim 1, furthercomprising: locating a tumor volume within the target tissue siteutilizing the sensor array.
 19. The method of claim 18, furthercomprising: positioning the sensor array to detect one of the tumorvolume or a boundary of the tumor volume.
 20. The method of claim 18,further comprising: positioning the energy delivery device within thelocated tumor volume to controllably ablate at least a portion of thetarget volume.
 21. The method of claim 1, further comprising:identifying a tumor boundary utilizing the sensor array.
 22. The methodof claim 21, further comprising: positioning the energy delivery devicerelative to the tumor boundary to controllably ablate at least a portionof a tumor volume.
 23. The method of claim 1, further comprising:determining an amount of tissue necrosis, coagulation, or injuryutilizing the sensor array.
 24. The method of claim 1, furthercomprising: determining a treatment end point utilizing the sensorarray.
 25. The method of claim 1, further comprising determining ahealthy tissue ablative margin responsive to an input from the sensorarray.
 26. The method of claim 25, wherein the input is at least one ofan optical input, a spectra, an absorbance spectra, a reflectancespectra, a change in reflectance, a change in absorbance, a tissue typeor a tissue property.
 27. The method of claim 25, further comprising:positioning the energy delivery device within the a tissue volumedefined by the healthy tissue margin, delivering energy from the energydelivery device to ablate or necrose tissue in the tissue volume definedby the health tissue margin.
 28. The method of claim 25, wherein thehealthy tissue margin is determined using logic resources coupled to thesensor array.
 29. The method of claim 25, wherein the logic resourcesare electronically coupled to a power source coupled to the energydelivery device.
 30. The method of claim 25, wherein the logic resourcesinclude at least one of a processor, a microprocessor, a softwaremodule, a fuzzy logic module, a database, a histological database, atumor database, or a database of prior ablations.
 31. The method ofclaim 30, further comprising: comparing an input from the sensor arrayto the database.
 32. The method of claim 1, further comprising:identifying at least one of a tissue type or a tissue property utilizingthe sensor array.
 33. The method of claim 32, wherein the tissueidentification is determined using logic resources coupled to the sensorarray.
 34. The method of claim 33, wherein the logic resources areelectronically coupled to a power source coupled to the energy deliverydevice.
 35. The method of claim 33, wherein the logic resources includeat least one of a processor, a microprocessor, a software module, afizzy logic module, a database, a histological database, a tissuedatabase or a tumor database.
 36. The method of claim 36, furthercomprising: comparing an input from the sensor array to the database.37. The method of claim 32, wherein the tissue type is one of a cancer,a metastatic cancer, a cyst, a tumor a coagulated tissue, an injuredtissue, a lysed tissue or a necrosed tissue.
 38. The method of claim 32,wherein the tissue property includes at least one of a physiologicproperty, a metabolic property, a genetic property, a thermal property,a temperature, an electrical property, an impedance, an opticalproperty, an absorbance, a reflectance, a hemoglobin saturation, adimensional property or a pH.
 39. The method of claim 32, furthercomprising: making a treatment decision based on information derivedfrom a tissue identification or a tissue property.
 40. The method ofclaim 32, further comprising: making one of a diagnosis or differentialdiagnosis based on the tissue property.
 41. The method of claim 32,further comprising making a differential diagnosis based on at least twotissue properties.
 42. The method of claim 39, wherein the treatmentdecision is at least one of a resection, a biopsy, an ablation, anenergy delivery, an amount of energy delivery, an energy delivery dutycycle, a drug delivery, an amount of drug delivery or a chemotherapeuticagent delivery.
 43. The method of claim 32, further comprising:titrating a tissue treatment based on information derived from a tissueidentification or a tissue property.
 44. The method of claim 39, whereinthe treatment is at least one of a resection, an ablation, an energydelivery, a drug delivery or a chemotherapeutic agent delivery.
 45. Themethod of claim 32, wherein the tissue property includes at least one ofa physiologic property, a metabolic property, a thermal property, atemperature, an electrical property, an impedance, an optical property,an absorbance, a reflectance, a dimensional property or a pH.
 46. Themethod of claim 1, further comprising: deploying the sensor array withina selectable tissue volume.
 47. The method of claim 1, furthercomprising: obtaining a baseline tissue property measurement of thetarget tissue utilizing the sensor array.
 48. The method of claim 47,further comprising: comparing the baseline property measurement to asecond tissue property measurement made during or after the delivery ofenergy to the target tissue.
 49. The method of claim 48, furthercomprising: adjusting an energy delivery parameter responsive to thecomparison of the baseline measurement to the second measurement. 50.The method of claim 49 further comprising: adjusting the energy deliveryparameter to enhance at least one of a tissue ablation time, a tissueablation volume or a thermal injury effect.
 51. The method of claim 49further comprising: adjusting the energy delivery parameter tocompensate for hysteresis, thermal hysteresis, electrical hysteresis,tissue desiccation, cell lysis or protein denaturization.
 52. The methodof claim 49, wherein the energy delivery parameter is one of a powerlevel, a power duty cycle, a current, a fluid flow rate, or anelectrolytic fluid flow rate.
 53. The method of claim 48, furthercomprising: making an treatment endpoint decision responsive to thecomparison of the baseline measurement to the second measurement. 54.The method of claim 49, wherein the adjustment is determined using logicresources coupled to the sensor array.
 55. The method of claim 49,wherein the logic resources are electronically coupled to a power sourcecoupled to the energy delivery device.
 56. The method of claim 49,wherein the logic resources include at least one of a processor, amicroprocessor, a software module, a fuzzy logic module, a database, ahistological database, a tissue database or a tumor database.
 57. Themethod of claim 1, further comprising: deploying a marking agent; andmarking at least one of a tumor volume, a tumor surface, an ablatedtissue volume, a hyperthermic tissue volume, or an injured tissuevolume.
 58. The method of claim 57, wherein tissue marking agent is oneof a tumor marker, a temperature sensitive marker, a fluorescent marker,a radioactive marker, an antibody, an antibody-coupled marker, aliposome, a liposome-coupled marker, an antibody-coated liposome, amicrosphere or a chemotherapeutic agent.
 59. The method of claim 57,wherein tissue marking agent includes a first marking agent and a secondmarking agent.
 60. The method of claim 59, wherein the first markingagent is configured to mark a first tissue condition and the secondmarking agent is configured to mark a second tissue condition.
 61. Themethod of claim 59, wherein the first marking agent is configured tomark a tumor condition and the second marking agent is configured tomark a thermal condition.
 62. The method of claim 59, wherein the firstmarking agent is configured to mark a first tissue temperature and thesecond marking agent is configured to mark a second tissue atemperature.
 63. The method of claim 57, wherein the marking agent isconfigured to enhance the delivery of energy to a least a portion of thetumor volume, the method further comprising: enhancing the delivery ofenergy to at least a portion of the tumor volume.
 64. The method ofclaim 63, wherein the at least a portion of the tumor volume isselectable.
 65. The method of claim 57, wherein the marking agent isconfigured to enhance the amount of thermal injury to a least a portionof the tumor volume, the method further comprising: enhancing thethermal injury to at least a portion of the tumor volume.
 66. The methodof claim 65, wherein the at least a portion of the tumor volume isselectable.
 67. The method of claim 57, wherein the sensor array isconfigured to detect a marking agent.
 68. The method of claim 67,wherein the sensor array is configured to obtain one of an improvedresolution or a sensitivity.
 69. The method of claim 57, furthercomprising a source of marking agent fluidically coupled to theelongated delivery device, the method further comprising: infusing themarking agent into the target tissue site.
 70. The method of claim 57,wherein the plurality of marking agents includes a first marking agentcoupled to a marking agent carrier, wherein the marking agent carrier isconfigured to release the first marking at a selectable temperature, themethod further comprising: releasing the marking agent in the targettissue site at a selectable temperature.
 71. The method of claim 70,further comprising: delivering energy from the energy delivery device torelease the marking agent.
 72. The method of claim 70, wherein theselectable temperature is in the range of about 40° C. to about 60° C.73. The method of claim 70, wherein the selectable temperature is in therange of about 45° C. to about 55° C.
 74. The method of claim 1, whereinthe geometric configuration is configured to detect one of a boundary ora volume of a tumor as at least a portion of the sensor array isadvanced into a target tissue site.
 75. The method of claim 1, whereinthe energy delivery device is one of an RF electrode, a monopolarelectrode or a bipolar electrode.
 76. The method of claim 1, wherein asource of RF energy is coupled to the RF electrode.
 77. The method ofclaim 1, wherein the sensor is one of an optical sensor, aphotomultiplier, an optical fiber, a ccd, a temperature sensor or achemical sensor.
 78. The method of claim 1, wherein the geometricconfiguration is substantially one of a hemisphere, sphere, oval, cone,pyramidal, a polyhedron or a tetrahedron.
 79. The method of claim 1,wherein at least one of the first or second resilient members isconfigured to have a changing direction of travel in tissue whenadvanced from the elongated delivery device to a selected tissue site.80. The method of claim 79, wherein at least the first resilient memberhas a first direction of travel and the second resilient member has asecond direction of travel.
 81. The method of claim 79, wherein at leastone of the first of the second resilient members has at least one of anelastic modulus, a bending modulus, a taper, a memory or a glasstransition temperature sufficient to produce a changing direction oftravel in response to a force applied by tissue.
 82. The method of claim1, wherein the sensor array is configured to differentiate tissue duringan energy delivery interval, a tissue desiccation condition, a tissuecharring condition or a tissue vaporization condition.
 83. The method ofclaim 1, wherein at least one of the resilient members includes aninfusion lumen and at least of the resilient members or the energydelivery device includes an infusion port, the method furthercomprising: infusing a fluid into the target tissue.
 84. The method ofclaim 83, wherein the fluid is one of an electrolytic solution, anelectrical conductivity enhancing solution, a thermally conductivityenhancing solution, an image contrast agent, an RF energy absorptionagent or an echogenic solution.
 85. The method of claim 1, wherein theat least one sensor is configured to detect a change in a tissueproperty.
 86. The method of claim 85, wherein the property includes atleast one of a physiologic property, a metabolic property, a thermalproperty, a temperature, an electrical property, an impedance, anoptical property, an absorbance, a reflectance, a dimensional propertyor a pH.
 87. The method of claim 1, wherein the sensor array isconfigured to detect least one of a tissue ablation volume, a tissuethermal volume or tissue hyperthermic volume.
 88. The method of claim 1,wherein the sensor array is configured to distinguish between cancerousand non-cancerous tissue.
 89. The method of claim 1, wherein the atleast one sensor includes a first sensor and a second sensor.
 90. Themethod of claim 89, wherein the at least one of the first or the secondsensors are positioned at a greater distance with the respect to alongitudinal axis of the elongated delivery device than the at least oneenergy delivery device.
 91. The method of claim 90, wherein the greaterdistance is at least one of a lateral or a longitudinal distance. 92.The method of claim 89, wherein at least one of the first or secondsensors is an emitter, an electromagnetic emitter, an acousticalemitter, an optical emitter, a laser or an LED.
 93. The method of claim92, wherein the emitter is substantially positioned within a volumedefined by the sensor array.
 94. The method of claim 92, wherein theemitter is substantially positioned within a volume defined by thesensor array.
 95. The method of claim 92, wherein the emitter emits areference signal and a probe signal.
 96. The method of claim 95, whereinthe at least one sensor includes a third sensor adapted to detect thereference signal.
 97. The method of claim 95, further comprising:employing the reference signal to compensate for a change in a tissuecondition at the tissue site, hysteresis, thermal hystereris, or opticalhysteresis.
 98. The method of claim 96, wherein the third sensor ispositioned substantially adjacent or in proximity to the emitter. 99.The method of claim 92, wherein the emitter is configured toelectromagnetic energy over a selectable frequency range.
 100. Themethod of claim 1, wherein the sensor array includes a third and afourth resilient member.
 101. A method of treating a tumor comprising:providing a tissue biopsy and treatment apparatus for detecting andtreating a tumor, the apparatus comprising an elongated delivery deviceincluding a lumen, the elongated delivery device being maneuverable intissue; a sensor array deployable from the elongated member, the sensorarray including a plurality of resilient members, at least one of theplurality of resilient members being positionable in the elongateddelivery device in a compacted state and deployable with curvature intotissue from the elongated delivery device in a deployed state, at leastone of the plurality of resilient members including at least one of asensor, a tissue piercing distal end or a lumen, the sensor array havinga geometric configuration adapted to volumetrically sample tissue at atissue site to differentiate or identify tissue at the tissue site; andat least one energy delivery device coupled to one of the sensor array,at least one of the plurality of resilient members or the elongateddelivery device; introducing the apparatus into a target site;maneuvering the energy delivery device through tissue responsive toinformation derived from the sensor array to ablate a tumor volume;delivering energy from the energy delivery device to ablate or necroseat least a portion of the tumor volume; and determining an amount oftumor volume ablation utilizing the sensor array.
 102. A method oftreating a tumor comprising: providing a tissue biopsy and treatmentapparatus for detecting and treating a tumor, the apparatus having asensor array positionable at a target tissue site, the sensor arrayincluding at least a first and a second resilient member, at least oneof the first or second resilient members including at least one of a asensor, a lumen, a sensor member positionable in the lumen, an energydelivery or a tissue piercing distal end; introducing the apparatus intothe target tissue site; positioning the sensor array at the targettissue site; utilizing the sensor array to make a first measurement of atissue parameter at the target site or retrieving a tissue parameter forthe target site from a database of tissue parameters; delivery energy tothe target tissue site; utilizing the sensor array to make a secondmeasurement of the tissue parameter during or after an energy deliveryinterval; comparing one of the first measurement or the retrievedparameter to the second measurement; and determining an amount of injuryor ablation of the target tissue volume utilizing a comparison betweenone of the first measurement or the retrieved parameter to the secondmeasurement.
 103. The method of claim 102, further comprising:determining a treatment endpoint.
 104. A method of treating a tumorcomprising: providing a tissue biopsy and treatment apparatus fordetecting and treating a tumor, the apparatus comprising an elongateddelivery device including a lumen, the elongated delivery device beingmaneuverable in tissue, a sensor array deployable from the elongatedmember, the sensor array including a plurality of resilient members, atleast one of the plurality of resilient members being positionable inthe elongated delivery device in a compacted state and deployable withcurvature into tissue from the elongated delivery device in a deployedstate, at least one of the plurality of resilient members including atleast one of a sensor, a tissue piercing distal end or a lumen, thesensor array having a geometric configuration adapted to volumetricallysample tissue at a tissue site to differentiate or identify tissue atthe tissue site; and at least one energy delivery device coupled to oneof the sensor array, at least one of the plurality of resilient membersor the elongated delivery device; distinguishing a tissue type utilizingthe sensor array means; positioning the energy delivery device meansutilizing tissue type information derived from the sensor array means toablate a tumor volume; delivering energy from the energy delivery deviceto ablate or necrose at least a portion of the tumor volume; anddetermining an amount of tumor volume ablation utilizing the sensorarray.